Cartridge hold-up volume reduction

ABSTRACT

Drug delivery systems with reduced hold-up volumes are provided. The drug delivery systems include a cartridge configured to hold a liquid drug. A cartridge stopper is positioned in a first portion of the cartridge. A needle guide component is positioned within the cartridge stopper. A needle is positioned within a central opening of the needle guide. A plunger is positioned in a second portion of the cartridge. The plunger includes a fluid path pocket facing and aligned with the central opening of the needle guide component. The plunger is driven toward the cartridge stopper to expel the liquid drug from the cartridge through the needle. An end of the needle can be positioned within the fluid path pocket when the plunger is pushed against the cartridge stopper, ensuring that only a small volume of the liquid drug remains in the cartridge when delivery of the liquid drug is completed.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Non-Provisional applicationSer. No. 15/875,115, filed Jan. 19, 2018, which claims the benefit ofU.S. Provisional Application No. 62/448,222, filed Jan. 19, 2017, U.S.Provisional Application No. 62/453,065, filed Feb. 1, 2017, and U.S.Provisional Application No. 62/549,488, filed Aug. 24, 2017, each ofwhich is incorporated herein by reference in its entirety.

TECHNICAL FIELD

Embodiments generally relate to medication delivery. More particularly,embodiments relate to reducing hold-up volume for drug delivery systems.

BACKGROUND

An on-body delivery system (OBDS) is often used to deliver drug dosagesto a user. Many OBDSs use cartridges to hold a liquid drug that isexpelled from the cartridge when a portion of the liquid drug is desiredto be delivered to the user. Many conventional OBDSs and associatedcartridges are not capable of delivering all of the stored liquid drugto the user. Specifically, relatively significant amounts of the liquiddrug can remain inside of the pre-filled cartridge when the OBDScompletes full delivery. The undelivered amount of the liquid drug iswasted and for expensive drugs can increase costs to various parties,including the user. Accordingly, there is a need for an OBDS, drugdelivery system and/or device, and/or cartridge having reduced amountsof a liquid drug remaining after delivery to reduce waste and reducecosts to various parties, including the user.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A illustrates a first view of a conventional drug delivery system.

FIG. 1B illustrates a second view of the conventional drug deliverysystem of FIG. 1A.

FIG. 2 illustrates a first view of a first exemplary drug deliverysystem.

FIG. 3 illustrates a second view of the first exemplary drug deliverysystem.

FIG. 4 illustrates a second exemplary drug delivery system.

FIG. 5 illustrates a first view of a third exemplary drug deliverysystem.

FIG. 6 illustrates a second view of the third exemplary drug deliverysystem.

FIG. 7 illustrates a first view of a fourth exemplary drug deliverysystem.

FIG. 8 illustrates a second view of the fourth exemplary drug deliverysystem.

FIG. 9 illustrates a third view of the fourth exemplary drug deliverysystem.

FIG. 10 illustrates a fourth view of the fourth exemplary drug deliverysystem.

DETAILED DESCRIPTION

This disclosure presents various systems, components, and methodsrelated to a drug delivery system and/or device. Each of the systems,components, and methods disclosed herein provides one or more advantagesover conventional systems, components, and methods.

Various embodiments provide drug delivery systems with reduced hold-upvolumes. The drug delivery systems include a cartridge configured tohold a liquid drug. A cartridge stopper is positioned in a first portionof the cartridge having a first diameter and forms a first seal for theliquid drug. A needle guide component is positioned within the cartridgestopper. A needle is positioned within a central opening of the needleguide. A plunger is positioned in a second portion of the cartridgehaving a second diameter, with the second diameter larger than the firstdiameter. The plunger forms a second seal for the liquid drug. Theplunger includes a fluid path pocket facing and aligned with the centralopening of the needle guide component. The needle pierces the cartridgestopper to be coupled to the liquid drug. The plunger is driven towardthe cartridge stopper to expel the liquid drug from the cartridgethrough the needle. An end of the needle can be positioned within thefluid path pocket when the plunger is pushed against the cartridgestopper, ensuring that only a small volume of the liquid drug remains inthe cartridge (e.g., within a portion of the fluid path pocket) whendelivery of the liquid drug is completed. As a result, a reduced amountof the liquid drug remains within the cartridge when delivery iscomplete.

FIG. 1A illustrates a conventional drug delivery system 100. The drugdelivery system 100 includes a drug container or cartridge 102. Thecartridge 102 can hold or store a liquid drug 104. A plunger 106 can bepositioned within the cartridge 102. A needle 108 can be positionedwithin the cartridge 102 and coupled to the liquid drug 104.

To expel the liquid drug 104 from the cartridge 102, the plunger 106 canbe moved in a direction 110 toward the needle 108. In doing so, theplunger 106 can force a portion of the liquid drug 104 through theneedle 108 and out of the cartridge 102. As the plunger 106 moves closerto the needle 108, more of the liquid drug 104 can be expelled from thecartridge 102.

FIG. 1B illustrates a subsequent stage of operation of the drug deliverysystem 100 relative to the depiction of the drug delivery system 100 inFIG. 1A. As shown in FIG. 1B, the plunger 106 is positioned adjacent toa neck of the cartridge 102 and cannot be advanced any further in thedirection 110. As a result, a portion of the liquid drug 104 remains inthe cartridge 102 as shown in FIG. 1B. That is, the liquid drug 104remaining in the cartridge 102 cannot be expelled from the cartridge 102by the plunger 106. The amount of space occupied by this portion of theliquid drug 104 that remains effectively trapped in the cartridge 102(or the amount or volume of the remaining liquid drug 104 itself) can beconsidered to be a hold-up volume (or portion thereof) of the cartridge102 and/or the drug delivery system 100. As will be appreciated by oneof ordinary skill in the art, in additional to the amount of space inthe cartridge 102, the entire fluid path (e.g., the needle) can also beconsidered to contribute to hold-up and/or to contribute to the hold-upvolume of the system.

Hold-up volume can represent the amount of space that can be occupied bya liquid drug that cannot be expelled and can include the volume ofliquid drug that cannot be expelled. As shown in FIGS. 1A and 1B, thearrangement and shapes of the components of the drug delivery system 100contribute to the size and shape of the resulting hold-up volume. Sincethe hold-up volume retains a portion of the liquid drug 104 that cannotbe expelled, reduction and minimization of the hold-up volume isdesirable. In general, the hold-up volume represents a wasted or unusedportion of the liquid drug 104. For very expensive drugs, the wastedamount of the liquid drug 104 can be very costly, which can be passedalong to the user, insurance company, or other purchaser of the drugdelivery system 100.

Since a portion of the stored liquid drug 104 may be trapped inside ofthe drug delivery system 100 (or at least not delivered to the user),then the amount of liquid drug 104 used to fill the cartridge 102 may begreater than the amount of liquid drug 104 that corresponds to the doseof the user. As explained above, this “over-filling” of the liquid drug104 for the user can add costs to the drug delivery system 100. Inaddition to this problem, air can be introduced into the drug deliverysystem 100 during typical filling processes associated with a pre-filleddevice such as the cartridge 102 and/or the drug delivery system 100.The introduced air is typically addressed in a number of ways. Forexample, the air may be purged out, which can add complexity and cost tothe drug delivery system and/or burden on the user. Alternatively, theair can be delivered to the user. Lastly, the air can be trapped withinthe drug delivery device 100.

Since a body-worn device (e.g., an OBDS) is multi-oriented, depending onwhere and how it is attached to the user's body, air will move withinthe container that stores a liquid drug (e.g., within the cartridge 102holding the liquid drug 104). In some instances, when air is trappedwithin the body-worn device and the outlet of the body-worn device isfacing down, gravity may cause the heavier liquid drug out of the deviceprior to the air. In other instances, when air is trapped within thebody-worn device and the outlet of the body-worn device is facing up,the air may be delivered first and a portion of the liquid drug maytrapped within the device as part of the hold-up volume. Because ofthese various orientations of the body-worn device and their impact onwhether air or liquid drug will be delivered to the patient, embodimentsas described herein improve dose accuracy by reducing hold-up volume.

Dose accuracy can be affected when the ratio of hold-up volume to fillvolume exceeds approximately 3-5%, with the dose accuracy being furthernegatively affected as this ration increases. For example, if a dosewithin 5% of 1 mL of a drug is desired using a device having a hold-upvolume of 0.2 mL, then the desired dose accuracy is not possible.Accordingly, in addition to reducing wastes, it is desired to reducehold-up volumes to achieve desired dosing accuracies and/or to achieveindustry standard dose accuracy requirements.

FIG. 2 illustrates a first exemplary drug delivery system 200 forproviding a reduced hold-up volume. The drug delivery system 200 canefficiently expel the liquid drug it contains while reducing amounts ofthe liquid drug retained by the drug delivery system 200 after use. Thereduced hold-up volume provided by the drug delivery system 200 canimprove dosing accuracy. FIG. 2 can represent a cross-sectional view ofthe drug delivery system 200. In various embodiments, the drug deliverysystem 200 can provide a ratio of hold-up volume to fill volume that isless 5% or less than 3%.

As shown in FIG. 2, the drug delivery system includes a drug containeror cartridge 202. In various embodiments, the cartridge 202 can be anInternational Organization for Standardization (ISO) standard cartridge202. In various embodiments, the cartridge 202 can be a custom design orcustomized cartridge 202. The cartridge 202 can comprise any suitablematerial such as, for example, metal, plastic, or glass, or anycombination thereof. The cartridge 202 can include a main body component204, a neck component 206, and a top component 208.

The cartridge 202 can generally be cylindrically-shaped with a diameterof the main body component 204 being substantially constant and largerthan a diameter of the top component 208. The neck component 206 canhave a variable diameter that transitions from a diameter correspondingto the diameter of the main body component 204 to the diameter of thetop component 208. The variable diameter portion of the neck component206 can be considered a transitional portion of the cartridge 202 wherethe wider main body component 204 transitions to the narrower topcomponent 208.

The top component 208 can be sealed by a septum 210 and a crimp 212. Theseptum 210 can be positioned adjacent to and/or over the top component208 (e.g., over an opening in the top component 208). The crimp 212 canbe positioned around the septum 210 and the top component 208 to tightlyfit the septum 210 against the top component 208. The septum 210 cancomprise any suitable material such as, for example, metal or plastic,or any combination thereof. The crimp 212 can comprise any suitablematerial such as, for example, metal or plastic, or any combinationthereof. The septum 210 and the crimp 212 can form at least one seal ofthe cartridge 202.

A second seal of the cartridge 202 can be formed by a plunger 214. Theplunger 214 can comprise any suitable material such as, for example,plastic or rubber. The plunger 214 can be positioned within the mainbody component 204. The plunger 214 can be positioned into the main bodycomponent 204 through an opening 216 of the cartridge 202.

A drug 218 can be stored or held in the cartridge 202. The drug 218 canbe a liquid drug. The drug 218 can be any therapeutic agent and/ormedicine. The drug 218 can be stored within the main body component 204.The plunger 214 can be positioned to retain or seal the liquid drug 218within the cartridge 202.

As further shown in FIG. 2, the drug delivery system 200 can alsoinclude a cartridge stopper 220. The cartridge stopper 220 can bepositioned within any portion of the main body component 204 and/or theneck component 206. In various embodiments, the cartridge stopper 220can be positioned within a portion of the neck component 206 and anadjacent portion of the main body component 204. The cartridge stopper220 can include a first side 222 that is substantially flat or planar.The first side 222 can be coupled to the liquid drug 218 and can befacing the plunger 214. The first side 222 can include a fluid pathpocket 224. The fluid path pocket 224 can comprise a hole or openingwithin the cartridge stopper 220, extending from the first side 222 intothe cartridge stopper 220. The fluid path pocket 224 can be positionedat an approximate center of the cartridge stopper 220 (e.g., alignedwith a center of the first side 222 and/or aligned with a central axisof the cartridge stopper 220).

A second side 226 of the cartridge stopper 220 can be shaped to fitwithin the transition region of the neck component 206. The second side226 can face the top component 208 of the cartridge 202. In variousembodiments, the second side 226 can be shaped to taper from arelatively wider diameter (e.g., a diameter of the main body component204) to a relatively narrower diameter (e.g., a diameter of thenarrowest portion of the neck component 206). The cartridge stopper 220can also form a seal for the liquid drug 218 as shown in FIG. 2. Thecartridge stopper 220 can be generally cylindrical-shaped and can beformed of any suitable material such as, for example, a plastic orrubber.

As shown in FIG. 2, an outer portion of the cartridge stopper 220 caninclude sealing features (e.g., sealing glands). In various embodiments,the cartridge stopper 220 can include any number of such sealingfeatures that can be varied based on application. As further shown inFIG. 2, the liquid drug 218 is retained within the cartridge 202 byseals provided by the cartridge stopper 220 and the plunger 214.

The drug delivery system 200 can further include a needle insertionguide 228. The needle insertion guide 228 can be generallycylindrically-shaped and can be positioned within the top component 208and the neck component 206. The needle insertion component 228 cancomprise any suitable material such as, for example, metal, stainlesssteel, plastic, or a polymer, or any combination thereof.

The needle insertion guide 228 can include an opening or hole 230. Theopening 230 can extend along an entire length of the needle insertionguide 228. The opening 230 can provide an area for a needle 232 to beguided through the top component 208 and the neck component 206. Toreach the liquid drug 218, the needle 232 can be inserted through thecrimp 212 and the septum 210 and into the opening 230 of the needleinsertion guide 228. The needle 232 can then be inserted further intothe cartridge 202 by subsequently piercing the cartridge stopper 220.Lastly, an end of the needle 232 can be inserted so as to be positionedwithin the fluid path pocket 224.

When the needle 232 is inserted with an end positioned within the fluidpath pocket 224, the plunger 214 can be used to expel the liquid drug218 from the cartridge 202. For example, the plunger 214 can be moved ina direction 234 toward the cartridge stopper 222. In doing so, theliquid drug 218 can be forced out of the cartridge 202 through theneedle 232. The plunger 214 can be advanced in the direction 234 untilthe plunger 214 is adjacent to the first side 222 of the cartridgestopper 220. By maintaining the end of the needle 232 within the fluidpath pocket 224, the plunger 214 can be pressed up against the firstside 222 without damaging the needle 232 or disturbing the positioningof the needle 232.

As shown in FIG. 2, the fluid path pocket 224 can be positioned with acenter of the cartridge stopper 220. In various embodiments, the fluidpath pocket 224 can be aligned with the opening 230 of the needleinsertion guide 228. This opening 230 guides the needle 232 such that asthe needle 232 is inserted further into the cartridge 202, the needle232 will reach the fluid path pocket 224.

FIG. 2 can represent a stage of operation of the drug delivery system200 prior to expelling the liquid drug 218 from the cartridge 202 (e.g.,prior to activation of the drug delivery system 200). As shown in FIG.2, the needle 232 has pierced the septum 210 and is partially insertedinto the needle insertion guide 228 but has not yet reached or piercedthe cartridge stopper 220. In a subsequent stage of operation, after theend of the needle 232 is inserted into the fluid path pocket 224, theplunger 214 can be advanced in the direction 234 to expel the liquiddrug 218 from the cartridge 202.

In various embodiments, the main body component 204 of the cartridge 202can have a first diameter that is substantially constant across anentire length of the main body component 204. Further, the top component208 and the neck component 206 of the cartridge 202 can have a smaller,second diameter. The neck component 206 can further include a regionthat transitions from the smaller or narrower region or portion of thecartridge 202 of the second diameter to the larger or wider region orportion of the cartridge 202 of the first diameter. In variousembodiments, the top component 208 and the neck component 206 cantogether be considered to be a necked area or the neck component 206 ofthe cartridge 202—which transitions from the larger, first diameter tothe smaller, second diameter.

FIG. 3 illustrates the drug delivery system 200 after expelling theliquid drug 218 from the cartridge 202. FIG. 3 can also represent across-sectional view of the drug delivery system 200. As shown in FIG.3, the needle 232 is inserted through the needle insertion guide 228 andthe cartridge stopper 220 such that the end of the needle 232 ismaintained within the fluid path pocket 224. The needle 232 can have ashape (e.g., a bend) and length that ensures the end of the needle 232is precisely positioned within the fluid path pocket 224 as shown. Theplunger 214 is positioned against the first side 222 of the cartridgestopper 220 and does not contact the needle 232 or disturb thepositioning of the needle 232. A hold-up volume 302 is shown in FIG. 3as highlighting an approximate amount of the liquid drug 218 thatremains inside the cartridge 202 (e.g., after no further liquid drug 218can be expelled by the plunger 214). Comparing the hold-up volume 302 tothe hold-up volume shown in FIG. 1B reveals that the drug deliverysystem 200 significantly reduces the amount of the liquid drug 218 thatremains inside of the cartridge 202, while also improving dose deliveryaccuracy.

As shown in FIG. 3, with the addition of the cartridge stopper 220, aportion of the neck component 206 is blocked off, thereby reducing theresulting hold-up volume 302 as discussed above. Positioning thecartridge stopper 220 within the necked area of the cartridge 202 canprovide a significant reduction in hold-up volume and increase in dosedelivery accuracy. The positioning of the cartridge stopper 220 can alsoincrease positional stability and provide space savings. Due to thereduced hold-up volume 302 provided by the drug delivery system 200, thedrug delivery system 200 can deliver any air volume without affectingdose tolerance (e.g., if any air is trapped within the cartridge 202 andexpelled by the plunger 214). This provides operational flexibilitysince the position of the plunger 214 does not need to be preciselycontrolled nor does any trapped air within the cartridge 202 need to bereduced to ensure accurate dosing of the liquid drug 218. Further, thesmaller hold-up volume 302 reduces and minimizes any wasted or unusedliquid drug 218 left within the cartridge 202. As previously mentioned,reducing the amount of wasted liquid drug 218 may reduce the cost of thedrug delivery system 200 for a user.

The drug delivery system 200 can be sterilized prior to use and beingprovided to a user in a variety of manners. In various embodiments, thedrug delivery system 200 can be sterilized with the needle 232 insertedbetween the septum 210 and the cartridge stopper 220 (e.g., as depictedin FIG. 2). Sterilization in this manner can provide a seal on theneedle 232 and can maintain sterility thereafter. In variousembodiments, the drug delivery system 200 can be sterilized with theneedle 232 partially inserted in the cartridge stopper 220.Sterilization in this manner can also provide a seal on the needle 232that can maintain sterility. In various embodiments, the drug deliverysystem 200 can be sterilized with the needle 232 completely removed fromthe cartridge 202 (i.e., separate from the cartridge assembly).

FIG. 4 illustrates a second exemplary drug delivery system 400. The drugdelivery system 400 is substantially similar to the drug delivery system200 in design and operation and represents an alternative design to thedrug delivery system 200. The drug delivery system 400 can providesubstantially the same benefits as the drug delivery system 200 asdescribed above. FIG. 4 can represent a cross-sectional view of the drugdelivery system 400. In various embodiments, the drug delivery system400 can provide a ratio of hold-up volume to fill volume that is less 5%or less than 3%.

As shown in FIG. 4, the drug delivery system 400 can include a cartridgestopper 402 having a fluid path pocket 404 on a first side and a secondside having an extended portion 406. The extended portion 406 can extendfurther into the neck component 206 of the cartridge 202. As also shownin FIG. 4, a needle insertion guide 408 of the drug delivery system 400can be substantially arranged and positioned within the top component208 of the cartridge 202. This alternative design and arrangement of thecartridge stopper 402 and the needle insertion guide 408 (e.g., incomparison to the cartridge stopper 220 and the needle insertion guide228, respectively) can provide increased sealing capabilities andadditional stability for the needle 232. In general, for any of the drugdelivery systems described herein that provide reduced hold-up volume,the cartridge stopper (e.g., the cartridge stopper 220 or 402) and theneedle insertion guide (e.g., the needle insertion guide 228 and 408)can be of any size and shape and can occupy any portions of the mainbody 204, the neck component 206, and/or the top component 208.

FIG. 5 illustrates a third exemplary drug delivery system 500 forproviding a reduced hold-up volume. As a result, the drug deliverysystem 500 provides efficient delivery of a stored liquid drug. FIG. 5can represent a cross-sectional view of the drug delivery system 500. Invarious embodiments, the drug delivery system 500 can provide a ratio ofhold-up volume to fill volume that is less 5% or less than 3%.

As shown in FIG. 5, the drug delivery system 500 can include many of thecomponents depicted and described in relation to the drug deliverysystem 200 and can further include a cartridge stopper 502, a plunger504, a needle insertion guide 506, an optional secondary needle seal508, and a needle 510. The cartridge stopper 502 can be positionedwithin a portion of the main body component 204 and the neck component206. The cartridge stopper 502 can have a first side 512 that issubstantially planar or flat that can be coupled to the liquid drug 218.The cartridge stopper 502 can provide a first seal for the liquid drug218 for containment within the cartridge 202. The cartridge stopper 502can be generally cylindrical-shaped and can be formed of any suitablematerial such as, for example, a plastic or rubber.

The plunger 504 can be positioned within the main body component 204.The plunger 504 can include a fluid path pocket 514. The fluid pathpocket 514 can comprise a hole or opening that extends partially intothe plunger 504 from a first side or surface 516 of the plunger 504. Thefluid path pocket 514 can be round or cylindrical in shape and can becentered about the plunger 504 (e.g., about a central axis of theplunger 504). The plunger 504 can form a second seal for the liquid drug218 for containment within the cartridge 202. The plunger 504 can begenerally cylindrical-shaped and can be formed of any suitable materialsuch as, for example, a plastic or rubber.

The needle insertion guide 506 can be positioned into the plunger 504from a second side or surface 518 of the plunger 504. In this way, theplunger 504 can provide stability for the needle insertion guide 506.The needle insertion guide 506 can include an opening or hole 520 thatextends through the needle insertion guide 506. The opening 520 can bealigned with the fluid path pocket 514 and can provide a guide forstabilizing and orienting the needle 510. Specifically, the needleinsertion guide 506 can ensure that an end of the needle 510 can bepositioned within the fluid path pocket 514 when the needle 510 is movedfurther in the direction 234. The needle insertion guide 506 cancomprise any suitable material such as, for example, metal, stainlesssteel, plastic, or a polymer, or any combination thereof.

The optional secondary needle seal 508 can be positioned in the mainbody component 204 between the plunger 504 and needle insertion guide506 and an end of the cartridge 202. The optional secondary needle seal508 can comprise any suitable materials such as, for example, rubber,plastic, or a polymer, or any combination thereof. The optionalsecondary needle seal 508 can provide a seal for the needle 510 forsterilization.

FIG. 5 can represent the drug delivery system 500 prior to activation orinitiation of expelling the stored liquid drug 218. When activated, theend of the needle 510 can be positioned in the fluid path pocket 514 byhaving the needle 510 move in the direction 234. The needle 510 canpierce and traverse a portion of the plunger 504 between the needleinsertion guide 506 and the fluid path pocket 514 in order to reach thefluid path pocket 514.

Once the end of the needle 510 is positioned within the fluid pathpocket 514, the plunger 504 (and the needle insertion guide 506 and theneedle 506) can be moved in the direction 234. As the plunger 504 ismoved towards the cartridge stopper 502, the liquid drug 218 can beexpelled out of the cartridge 202 through the needle 510. The drugdelivery system 500 enables the liquid drug 218 to be expelled out of anopposite end of the cartridge 202 as compared to the end of thecartridge 202 from which the liquid drug 218 is expelled by the drugdelivery system 200.

As described above, the fluid path pocket 514 can be positioned within acenter of the plunger 504. The fluid path pocket 514 can have anycross-sectional shape such as, for example, circular or rectangular. Thefluid path pocket 514 can have a depth 522—that is, the fluid pathpocket 514 can extend a distance 522 into the plunger 504 from the firstsurface 516 of the plunger 504.

The needle insertion guide 506 can include a base component 524 and anextension component 526. The base component 524 can extend into theplunger 504 by a first distance 528 and the extension component 526 canextend into the plunger 504 by an additional second distance 530 beyondthe first distance 528. The base component 524 can be substantiallyflush with the second surface 518 of the plunger 506.

In various embodiments, the needle insertion guide 506 can be arrangedand/or shaped in different manners. For example, the needle insertionguide 506 can be positioned adjacent to the second surface 518 of theplunger 502 rather than being inserted into a portion of the plunger504. In such embodiments, the needle insertion guide 506 may besubstantially cylindrical having a substantially uniform thickness.

FIG. 6 illustrates the drug delivery system 500 after expelling theliquid drug 218 from the cartridge 202. FIG. 6 can also represent across-sectional view of the drug delivery system 500. As shown in FIG.6, the needle 510 is inserted through the needle insertion guide 506 andthe plunger 504 such that the end of the needle 510 is maintained withinthe fluid path pocket 514. The plunger 504 is positioned against thefirst side 512 of the cartridge stopper 502 without the cartridgestopper 502 contacting the needle 510 or disturbing the positioning ofthe needle 510. A hold-up volume 602 is shown in FIG. 6 as highlightingan approximate amount of the liquid drug 218 that remains inside of thecartridge 202. Comparing the hold-up volume 602 to the hold-up volumeshown in FIG. 1B reveals that the drug delivery system 500 significantlyreduces the amount of the liquid drug 218 that remains inside of thecartridge 202, while also improving dose delivery accuracy.

The drug delivery system 500 can be sterilized prior to use and beingprovided to a user in a variety of manners. In various embodiments, thedrug delivery system 500 can be sterilized with the needle 510positioned within the needle insertion guide 506 but not coupled to theliquid drug 218. In such embodiments, the optional secondary needle seal508 can be used to maintain sterility of the needle 510 from the endpositioned in the needle insertion guide 506 to the portion of theneedle 510 adjacent the optional secondary needle seal 508. In variousembodiments, the drug delivery system 500 can be sterilized with theneedle 510 partially inserted into the plunger 504 (e.g., with the endof the needle 510 positioned in the plunger 504 prior to reaching thefluid path pocket 514). In various embodiments, the drug delivery system500 can be sterilized with the needle 510 inserted into the fluid pathpocket 514 and coupled to the liquid drug 518. In such embodiments, aneedle seal at the opposite end of the needle can be used to seal theneedle path.

The drug delivery system 500, by incorporating rear piercing of theplunger 504, can reduce the overall size of the drug delivery system 500by obviating the need for delivery mechanisms positioned near a frontend of the cartridge 202 (e.g., near the top component 208). In variousembodiments, the drug delivery system 500, as depicted in FIGS. 5 and 6,can provided without the septum 210 and the crimp 212.

FIG. 7 illustrates a fourth exemplary drug delivery system 700. The drugdelivery system 700 can include certain features that are substantiallysimilar to the drug delivery system 200 as shown. The drug deliverysystem 700 can operate in a similar manner to the drug delivery system200 while representing an alternative design to the drug delivery system200. The drug delivery system 700 can provide substantially the samebenefits as the drug delivery system 200 as described above. FIG. 7 canrepresent a cross-sectional view of the drug delivery system 700. Invarious embodiments, the drug delivery system 700 can provide a ratio ofhold-up volume to fill volume that is less 5% or less than 3%.

As shown in FIG. 7, the drug delivery system 700 includes a cartridgestopper 702. The cartridge stopper 702 can be formed from any suitablematerial such as, for example, plastic or rubber. The cartridge stopper702 can be positioned with a portion of the neck component 206 and/orthe top component 208. In various embodiments, the cartridge stopper 702can be positioned so as not to extend beyond the position of the neckcomponent 206 having a substantially constant diameter (i.e., to not bepositioned within the transition region of the neck component 206). Thecartridge stopper 702 can be cylindrically-shaped to tightly fit withinthe diameter of the neck component 208 (e.g., the smallest diameter ofthe cartridge 202). In various embodiments, the cartridge stopper 702can be positioned within the neck component 208 using an interferencefit or press fit. The cartridge stopper 702 can help seal the liquiddrug 218 within the cartridge 202 such that, for example, the liquiddrug 218 does not contact the septum 210. As shown in FIG. 7, thearrangement and positioning of the cartridge stopper 702 allows aportion of the liquid drug to extend into the neck component 206 of thecartridge 202.

The drug delivery system 700 can further include a needle insertionguide component 704. The needle insertion guide component 704 can bepositioned within the cartridge stopper 702. In various embodiments, thecartridge stopper 702 can have an opening (e.g., a partially hollowcenter portion or cavity) that allows the needle insertion guidecomponent 704 to be positioned into the cartridge stopper 702 to betightly sealed and retained therein. The needle insertion guidecomponent 704 can be formed of any suitable material such as, forexample, metal, stainless steel, rubber, plastic, or a polymer, or anycombination thereof. The needle insertion guide component 704 can becylindrically-shaped and can be positioned entirely within the cartridgestopper 702.

A needle 706 can be positioned with the needle insertion guide component704. The needle insertion guide component 704 can include an opening orhole 708 that extends the length of the needle insertion guide component704. The needle 706 can be positioned within the opening 708. Theopening 708 can provide a guide for the needle 706. The opening 708 canhave a first conical portion (positioned closer to the top component208) and a cylindrical portion (positioned closer to the main bodycomponent 204) as shown in FIG. 7. The opening 708 can be positionedalong a center of the needle insertion guide component 704 (e.g., alonga central axis of the needle insertion guide component 704).

The drug delivery system 700 can further include a plunger 720. Theplunger 720 can be formed of any suitable material such as, for example,plastic or rubber. The plunger 720 can form another seal for the liquiddrug 218. The liquid drug 218 can be accessed by the needle 706.Specifically, the needle 706 can be moved to pierce the cartridgestopper 702 to access the liquid drug 218. After piercing the cartridgestopper 702 to access the liquid drug 218, an end of the needle 706 canbe positioned within the neck component 206 in fluid communication withthe liquid drug 218.

As shown, the plunger 720 can have a first side or surface 712 and asecond side or surface 714. The first side 712 can be substantiallyplanar or flat and can face the opening 216 of the cartridge 202. Thesecond side 714 can have a surface 716 that extends at an angle from aside of the plunger 720. The side of the plunger 720 can include one ormore seal features and can be substantially cylindrical in shape. Thesurface 716 can extend from the side of the plunger 720 at an angle to afluid path pocket area or component 718. The second surface 714 of theplunger 720 can be shaped to approximately match a shape of the neckcomponent 206—in particular, a transition region of the neck component206.

The fluid path pocket 718 can be a hole or opening that extends into theplunger 720 (e.g., partially into the plunger 720 from the second side714) by a distance or depth 710. The fluid path pocket 718 can have anyshape such as, for example, circular or square. The fluid path pocket718 can have a decreasing diameter moving in a direction from the secondside 714 to the first side 712. The fluid path pocket 718 can bepositioned about a center of the plunger 720 (e.g., along a central axisof the plunger 720).

The fluid path pocket 718 can be aligned with the opening 708 of theneedle insertion guide component 704. In this way, when the needle 706pierces through the cartridge stopper 702 and is coupled to the liquiddrug 218, an end of the needle 706 will align with the fluid path pocket718. This enables the plunger 720 to be pushed into the transition areaof the neck component 206 without damaging the needle 706 or itsposition, as the end of the needle 706 is secured within the fluid pathpocket 718 and does not contact the plunger 720. Precise positioning ofthe end of the needle 706 can be controlled by a number of mannersincluding, for example, a shape of the needle 706—for example, byincluding a bend or turn in the needle 706 to limit how far the needle706 can extend into the cartridge 202.

To expel the liquid drug 218 from the cartridge 202, the plunger 720 canbe advanced in the direction 234 toward the cartridge stopper 702. Asthe plunger 720 is advanced, the liquid drug 218 can be forced out ofthe cartridge 202 through the needle 706.

As shown in FIG. 7, the cartridge stopper 702 blocks off a portion ofthe neck component 206. The size, arrangement, and positioning of thecartridge stopper 702, along with the shape of the plunger 720, canprovide reduced hold-up volume and an increase in dose deliveryaccuracy. Further, the cartridge 202 can be filled using standard filland finishing processes with standardized equipment and can be filledwith the liquid drug from the opening 216 (e.g., before installing theplunger 720). Compared to the drug delivery system 200, the drugdelivery system 700 can be made shorter in length while holding anddelivering the same amount of liquid drug 218. As a result, an on-bodydelivery system (e.g., an insulin pump) holding the drug delivery system700 can be made shorter in length.

In various embodiments, the cartridge stopper 702 can be considered asincluding a central opening or cavity for accepting the needle guidecomponent 704. The needle guide component 704 can be tightly pressed orfitted into the cavity of the cartridge stopper 702, so that thecartridge stopper 702 is tightly positioned around the needle guidecomponent 704 and against the cartridge 202 to form a seal for theliquid drug 218.

The cartridge stopper 702 can be considered to be disposed or positionedwithin a first region or portion of the cartridge 202. This first regionor portion of the cartridge 202 can have a first diameter. In contrast,the plunger 720 can be considered to be positioned within a secondregion or portion of the cartridge 202. This second region or portion ofthe cartridge 202 can have a second diameter, with the second diameterbeing larger than the first diameter. The cartridge 202 can furtherinclude a region or portion where the cartridge 202 transitions from thefirst diameter to the second diameter. As shown in FIG. 7, the plunger720 can be shaped to approximately match the boundaries of thistransition region. Further, the diameter of the cartridge stopper 702can approximately match the first diameter of the cartridge 202 and thediameter of the plunger 720 can approximately match the second diameterof the cartridge 202.

In various embodiments, as further described herein, the opening 708 ofthe needle guide component 704 can be aligned with the fluid path pocket718. In various embodiments, the opening 708 can be aligned with acenter of the fluid path pocket 718. In various embodiments, the opening718 and the fluid path pocket 718 can be aligned and/or centered about asame central axis of either component and/or the cartridge 202.

FIG. 8 illustrates a close-up view of a portion of the drug deliverysystem 700. As shown in FIG. 8, the needle 706 can be stored in theposition show—that is, the needle 706 can be positioned within theneedle insertion guide component 704 without piercing the cartridgestopper 702 so as to access the liquid drug 218. When the drug deliverysystem 700 is activated, a needle insertion mechanism (not shown in FIG.8) can advance the needle 706 into the neck component 206 to be coupledwith the liquid drug 218.

A sterile zone 802 represents a sterile area of the drug delivery system700. The needle 706, as shown, can be stored prior to activation of thedrug delivery system 700 within the sterile zone 802. The drug deliverysystem 700 can be sterilized after the needle 706 is inserted into theposition as shown in FIG. 8. The sterile zone 802 can remain sealed andsterile prior to use.

As further shown in FIG. 8, the opening 708 of the needle insertionguide component 704 can include a first conical portion 804 (positionedcloser to the top component 208) and a second cylindrical portion 806(positioned closer to the main body component 204). The needle insertionguide component 704 can be fully positioned within an inner portion(e.g., opening) of the cartridge stopper 702.

The cartridge stopper 702 can include a first portion 808 (positionedadjacent to the septum 210) and a second portion 810 (positionedadjacent to the liquid drug 218). During storage and/or prior toactivation of the drug delivery system 700, the needle 706 can bepositioned as shown in FIG. 8—for example, positioned through the firstportion 808 and adjacent to the second portion 810 (but not yet havingpierced the second portion 810). The needle 706 can be advanced towardthe second portion 810 and can pierce the second portion 810 when thedrug delivery system 700 is activated, thereby coupling the needle 706to the liquid drug 218. The needle insertion guide component 704 canprovide accurate guiding of needle 706 through the cartridge stopper702.

FIG. 9 illustrates the drug delivery system 700 after activation.Specifically, FIG. 9 illustrates the drug delivery system 700 after theneedle 706 has been advanced toward the liquid drug 218. FIG. 9 alsoillustrates a close-up view of a portion of the drug delivery system700. As the needle 706 is advanced, the end of the needle 706 piercesand extends through the second portion 810 of the cartridge stopper 702.The end of the needle 706 extends just beyond the cartridge stopper 702and is coupled to the liquid drug 218. The needle insertion guidecomponent 704 provides accurate alignment of the needle 706 through thecartridge stopper 706 (e.g., to maintain alignment of the needle 706with the central axis of the cartridge stopper 706).

Once the needle 706 is advanced into the cartridge 202 as shown in FIG.9, the plunger 720 (as shown in FIG. 7) can be advanced in the direction234 to expel the liquid drug 218 out of the cartridge 202 through theneedle 706. In various embodiments, the thickness of the second portion810 of the cartridge stopper 702 can maintain sterility andnon-permeability prior to being pierced by the needle 706. For example,the second portion 810 of the cartridge stopper 706 can have a thicknessof at least 1.5 mm to maintain closure integrity of the container 202.

FIG. 10 illustrates the drug delivery system 700 after substantially allof the liquid drug 218 has been expelled from the cartridge 202. FIG. 10also illustrates a close-up view of a portion of the drug deliverysystem 700. As shown, the end of the needle 706 is positioned within thefluid path pocket 718. The needle insertion guide component 704 ensuresthe end of the needle 706 is aligned with the fluid path pocket 718. Theplunger 720 is positioned against the cartridge stopper 702. The plunger720 is also pressed against the neck component 206 such that the surface716 is pressed against the transitional portion of the neck component206—with a portion of the surface 716 surrounding the fluid path pocket718 adjacent to or pressed against the cartridge stopper 702 as shown.

A hold-up volume 1002 is shown in FIG. 10 as highlighting an approximateamount of the liquid drug 218 that remains inside of the cartridge 202.Comparing the hold-up volume 1002 to the hold-up volume of FIG. 1Breveals that the drug delivery system 700 significantly reduces theamount of the liquid drug 218 that remains inside of the cartridge 202,while also improving dose delivery accuracy. The positioning of theneedle 706, in terms of concentricity (e.g., with respect to thecartridge 202) and depth (e.g., with respect to the neck component 206)can be controlled to leave a relatively small hold-up volume 1002. Asfurther shown, the needle 706 is positioned such that at the end of theplunger stroke (e.g., when the plunger 720 is positioned as far againstthe neck component 206 as possible), the needle 706 remains in the fluidpath pocket 718.

The drug delivery system 700 provides further advantages in that thedrug delivery system 700 provides a reduced amount of surface area fromthe cartridge stopper 702 and the plunger 720 that may contact theliquid drug 218 (e.g., in comparison to the other drug delivery systemsdescribed herein that have larger combined surface areas in contact withthe liquid drug 218 due to the increased surface area of the cartridgestoppers used therein). In various embodiments, the cartridge stopper702 and the plunger 720 can be formed from an elastomer. Leachable andextractable levels of a drug can result when a liquid drug is in contactwith an elastomer, which can adversely affect the drug and/or adverselyaffect drug stability. Accordingly, the reduced surface area of thecartridge stopper 702 and the plunger 720 (e.g., combined or in total)provided by the drug delivery system 700 can improve stability of theliquid drug 218.

Any of the individual drug delivery systems described herein (e.g., drugdelivery systems 200, 400, 500, and 700) and/or any features thereof canbe combined with any other drug delivery system and/or feature thereof.

The following examples pertain to additional further embodiments:

Example 1 is a drug delivery system comprising a cartridge configured tohold a liquid drug, a cartridge stopper positioned in a first portion ofthe cartridge having a first diameter, a needle guide componentpositioned within the cartridge stopper, a needle positioned within acentral opening of the needle guide, and a plunger positioned in asecond portion of the cartridge having a second diameter, the seconddiameter larger than the first diameter, the plunger having a fluid pathpocket facing and aligned with the central opening of the needle guidecomponent.

Example 2 is an extension of example 1 or any other example disclosedherein, wherein the cartridge is an International Organization forStandardization (ISO) cartridge.

Example 3 is an extension of example 1 or any other example disclosedherein, wherein the cartridge stopper is formed from plastic or rubber

Example 4 is an extension of example 1 or any other example disclosedherein, wherein the cartridge stopper is cylindrically-shaped.

Example 5 is an extension of example 4 or any other example disclosedherein, wherein the cartridge stopper has a diameter approximatelymatching the first diameter, the cartridge stopper configured to form aseal for the liquid drug.

Example 6 is an extension of example 5 or any other example disclosedherein, wherein the cartridge stopper includes a central cavityconfigured to retain the needle guide component.

Example 7 is an extension of example 6 or any other example disclosedherein, wherein the needle guide component is formed from metal,plastic, or rubber.

Example 8 is an extension of example 7 or any other example disclosedherein, wherein the needle guide component is configured to be fittedwithin the central cavity of the cartridge stopper.

Example 9 is an extension of example 8 or any other example disclosedherein, wherein the central opening of the needle guide componentincludes a conical portion and a cylindrical portion.

Example 10 is an extension of example 9 or any other example disclosedherein, wherein the cylindrical portion is positioned closer to theplunger.

Example 11 is an extension of example 10 or any other example disclosedherein, wherein the central opening of the needle guide component isaligned with a central axis of the needle guide component.

Example 12 is an extension of example 11 or any other example disclosedherein, wherein the central opening of the needle guide component isaligned with a center of the fluid path pocket.

Example 13 is an extension of example 1 or any other example disclosedherein, wherein the plunger includes a first surface facing an openingof the cartridge and a second surface facing the cartridge stopper, thesecond surface containing the fluid path pocket, the plunger forming aseal for the liquid drug.

Example 14 is an extension of example 13 or any other example disclosedherein, wherein the first surface is substantially planar.

Example 15 is an extension of example 13 or any other example disclosedherein, wherein the plunger has a diameter approximately matching thesecond diameter.

Example 16 is an extension of example 13 or any other example disclosedherein, wherein the fluid path pocket is cylindrically-shaped.

Example 17 is an extension of example 13 or any other example disclosedherein, wherein the fluid path pocket has a depth that extends into theplunger from the second surface.

Example 18 is an extension of example 17 or any other example disclosedherein, wherein the fluid path pocket comprises a decreasing diameteralong the depth of the fluid path pocket.

Example 19 is an extension of example 17 or any other example disclosedherein, wherein the second surface is angled from a side of the plungertoward the fluid path pocket.

Example 20 is an extension of example 19 or any other example disclosedherein, wherein the second surface is shaped to approximately match atransition region of the cartridge, the transition region of thecartridge having a variable diameter that transitions from the firstdiameter to the second diameter.

Example 21 is an extension of example 13 or any other example disclosedherein, wherein the needle is configured to pierce the cartridge stopperto be coupled to the liquid drug.

Example 22 is an extension of example 21 or any other example disclosedherein, wherein the plunger is configured to be driven toward thecartridge stopper to expel the liquid drug out of the cartridge throughthe needle.

Example 23 is an extension of example 22 or any other example disclosedherein, wherein an end of the needle is configured to be positionedwithin the fluid path pocket of the plunger when the plunger expelssubstantially all of the liquid drug from the cartridge.

Example 24 is an extension of example 22 or any other example disclosedherein, wherein an end of the needle is configured to be positionedwithin the fluid path pocket of the plunger when the second surface ofthe plunger is pressed against the cartridge stopper.

Example 25 is an extension of example 24 or any other example disclosedherein, wherein the end of the needle is not in contact with theplunger.

Example 26 is an extension of example 1 or any other example disclosedherein, wherein the needle guide component is formed from a metal.

Certain embodiments of the present invention were described above. Itis, however, expressly noted that the present invention is not limitedto those embodiments, but rather the intention is that additions andmodifications to what was expressly described herein are also includedwithin the scope of the invention. Moreover, it is to be understood thatthe features of the various embodiments described herein were notmutually exclusive and can exist in various combinations andpermutations, even if such combinations or permutations were not madeexpress herein, without departing from the spirit and scope of theinvention. In fact, variations, modifications, and other implementationsof what was described herein will occur to those of ordinary skill inthe art without departing from the spirit and the scope of theinvention. As such, the invention is not to be defined only by thepreceding illustrative description.

What is claimed is:
 1. A drug delivery system, comprising: a cartridgeconfigured to hold a liquid drug; a cartridge stopper positioned in afirst portion of the cartridge and including a fluid path pocket; aneedle insertion guide positioned adjacent to the cartridge stopper,wherein the needle insertion guide has an opening aligned with the fluidpath pocket; and a plunger positioned in a second portion of thecartridge and operable to advance through the cartridge in a directionof the cartridge stopper.
 2. The drug delivery system of claim 1,wherein the cartridge stopper is formed from plastic or rubber.
 3. Thedrug delivery system of claim 1, wherein the cartridge stopper iscylindrically-shaped.
 4. The drug delivery system of claim 1, whereinthe cartridge stopper has a shape operable to fit within a transitionregion of a neck component of the cartridge, and the cartridge stopperis operable to form a seal for the liquid drug.
 5. The drug deliverysystem of claim 1, wherein the needle insertion guide is formed frommetal, plastic, or rubber.
 6. The drug delivery system of claim 1,wherein the opening of the needle insertion guide extends along anentire length of the needle insertion guide.
 7. The drug delivery systemof claim 6, wherein the opening of the needle insertion guide includes aconical portion and a cylindrical portion.
 8. The drug delivery systemof claim 1, wherein the plunger includes a first surface facing thecartridge stopper and a second surface facing an opening of thecartridge, the first surface positioned to contact a liquid drug in thecartridge, and the plunger forms a seal with the cartridge for theliquid drug.
 9. The drug delivery system of claim 8, wherein the firstsurface of the plunger and the second surface of the plunger aresubstantially planar.
 10. The drug delivery system of claim 1, whereinthe fluid path pocket is cylindrically-shaped.
 11. The drug deliverysystem of claim 1, wherein the cartridge stopper has a second sideangled to match a neck component of the cartridge.
 12. The drug deliverysystem of claim 1, wherein the cartridge stopper has a second side andthe fluid path pocket has a depth that extends into the cartridgestopper from a first side.
 13. The drug delivery system of claim 1,further comprising: a needle operable to deliver a liquid drug, whereinthe needle is positioned within an opening of the needle insertion guideand operable to reach the fluid path pocket when inserted into thecartridge and through the cartridge stopper to the fluid path pocket.14. The drug delivery system of claim 13, wherein the needle furthercomprises: a shape and a length operable to position an end of theneedle within the fluid path pocket.
 15. The drug delivery system ofclaim 14, wherein the plunger when positioned against a first side ofthe cartridge stopper does not contact or disturb the positioning of theneedle.
 16. The drug delivery system of claim 13, wherein the plungerincludes a first surface facing the cartridge stopper and an end of theneedle is configured to be positioned within the fluid path pocket ofthe cartridge stopper when the first surface of the plunger contacts thecartridge stopper.
 17. The drug delivery system of claim 1, wherein theplunger is configured to be driven toward the cartridge stopper to expelthe liquid drug out of the cartridge through the needle.
 18. The drugdelivery system of claim 1, further comprising: a crimp and a septum,wherein the crimp is positioned around the septum and a top component ofthe cartridge and is operable to tightly fit the septum against the topcomponent.
 19. The drug delivery system of claim 18, wherein the crimpand septum are positioned over an opening to the needle insertion guideand are operable to be pierced by a needle during insertion of theneedle into the needle insertion guide.
 20. The drug delivery system ofclaim 18, wherein the needle insertion guide is positioned between theseptum and the cartridge stopper.